Mgnoetherification of mono-tertiary-



United States Patent "ice? MONOETHERIFICATION F MONO-TERTIARY USING A -HYDR O-.-m CARBON SOLVENT Milfoii of 'Newtalersey No Drawing. Application April 23, 1953',

Serial'Nd.350763"' 2 Glaiinst 1 c1; 260*61-3) This iinventionr relates to a process for preparin'g a sub'sramiallyuquantitive yieldwof Ia: mixture of moreithan about l two parts of a Z-tertiai-yhutyI- l-alkoxyphenol' to-- geth'er with one' part: of a; 3-terti-arybutyl 4 alkoxyphenol, which process comprises reacting at an e'levated ternperm '11 ture mono tenianybutyl iiydrdquinone rwith a dialkyl Sui-r.

compriaing -a non-aqueous liquid phase containing a hydroearbon solvent or any I other f inert water-immisciblephase maintained I in an alkaline condition during the course -of the; reaction." 1

One procedure-nowbeing-usedfor the preparationof the 't'wo isoniers of ter-tiarybutyl-4 alkoiiyphen01sinvolves the reaetion" of hydroq-uinone with 3 a methylating agent to "obtain 4-nietl'ioiiyphenohfollovved by alkylatioNof-the lat'ter 'witlr a source of the 'tertiat'ybutyl"radieal' s'uch as E isobut'ylene"*or tertiarybutyl alcohol? This process and the inheren'tdisadvantages involved are discussed-in a copendin'g application Serial" N01 277, 508; filed on March 19f195-2fby Young et a-Lfentitled Preparation of-Ter In -the"Yoiing'et al application a' new proces'sis disclosed" for the preparation of tertiarybutyl hydroquinoneem ploying 'an aromatichydrocarbon'solvent to facilitate the reaction whereby i the i end product consists substantially of "the mono-tertiarybutylderivative. The'YOun -"et 'a'l application also "disclosesa process" for the" preparation of a mixture of a major proportion of Z-t'rtiarybutyl-A metho'Xyp'honol ancl a minor proportion of ""3-t'ertia'rybutyl t rriethoxypheiiol by reacting at an elevated tern perature"mono tertiarybutyl hydroquinone with Himeth aqueous alkaline "solution containing at leastabout 0.1

percent of comminuted' zinc under an inert atmosphere; The*processdisclosed'by Young'et' a1 represented'a' major advarice. over "thepriori art; however, as "indicated in Example -o in the'Ymin'g et al.application,"the'product" obtained representedonly .about a percent conversion of n'ionoqertiarybutyl hydroquinoneto mono-tertiarybu tyl' 4-liydro'xy' 'anisole "of "the "following composition:

Pei-cent 3-tertiarybut yl= -hydroxyr anisoleuz-uua 79.4 2-te'rtiarybutyl 4 hydroxyaanisole; 17.6

Of the imon'o tetriarybutyl" hyclrdquinone" employed "by" Young et al in their Example 6 as a startingmate'ria'li thei'ejremained' in the reaction'product 236 ercent which'hati' not entered into"the .reactionfin addition; a

little over one'percent'of the starting material was converted to the dimethyl ether .of mono tertiarybutylhy drdquinone:

Although theYoiinget a1 process represents a substantial improvementovertheprior art-processyit is obvious ly morepracticaland'econoniiczfl from an =operat1o'nal standpoint to make use of substantially 'all of the monotertiarybut yl hydroquinone employed' as the starting materials In 'order f to do' s'o'by the process disclosed by Young et al it would-be necessary to either (1) recover the unreacted material from the reactionl product and! empl'oy it in a-'subsequent reaction or (2) employ much larger amounts of the ether ification agent in which: event the reaction product would *contain much larger -amounts-i r of the undesirable; 'dimethyl ether of the mono-tertiary-b butyl Hydroquinonem As a'n unexpected improvementover the'Young-et a1 process and" as a clearly marked advanced over theprior art discussed in the young et-alapplicatiom fl-havenow found that byusin'g a' solvent g such -as an-aliphatioor 1 aromati'c ihydrocarbongin l association with the aqueous ethe'rifi'cationi medium-of Youn'g' et ali thatagreatly improved yield of the desired mono-teriarybutyl 4 a1koxy phenols -"resultsi 5 1 1 Moreover; the reaction product contains'*-a- -clearly predoniin'ant proportion of the more potent antioxidaiiflisomer 2-tertiarybutyl l-alkoxyphenol, with acorresponding reductien 'in the fori'nation of-the' undesirable dialkyl ether of nio'no 'ter'iarybutyl hydroquii nOneH 'Fu'ItI'l'eimOre, the' mono-tertiarybutyl hydroqui nonsta-rting rnaterial is substantially completely convert'eci-t'c$ for'rn th monoethrsi Arr-objectofthisinvention is to -provide a process for etheri'fying'*mono tertiarybutyl-hydroquinone whereby a substantially*quantitive yield-of monoalkyl ethers is produ'ced; "An additional object orrny invention is to pro videsuch-a process" wherein the ratio of '2-tert-iar'ybutyl 4 -"-aIkoxyphe1io1s-'to 3--' tertiarybutyl 4 --alkox'y'phenols is greater-tha'ri'tivoto one; Another-objectis to provide a processwhih substantially eliminates the necessity for recoveringwnuseti starting material from the reaction mixture thereby greatly"*itnproving the economical andoperational aspects-*of the preparation-of desirable anti- I oxidantsl In "broa'dfi'ern'ismyfinvention-provides a process for I preparinga' substantiallyquantitive yield of 'a mixture of a protective materiarina medium comprising a nonaqueous liquidipha's'e containing "a' solvent "selected from the"g roup consistingot aliphatic and aromatic hydrocarboiis containi'ng ifrorrr'aboufS to about 10 carbon atomsandah'a ueous liquid phase maintained in an alka-l line-"condition dur'ingthe' course' of the reaction.

Thetemperature at Whic'h'theprocess is conducted is: advantageously: tromabont 50to about C. More.

advantageously, theprefe'rred temperaturer'ange is from] about 75 to aboutl00" C.-in Which range satisfactory reactioii'bccurs' in a reasonable length of'time." Still more advantageous'ly'the reaction is conducted under 'reflux conditions whichautoir'iatically 'governs' the temperatureofthe reaction dependingupon the nature of the reaction medium and the concentra'tio'n'of reactants and,

reaction products thereinJThere is nothing critical about'thetemperature employed. Moreover,-the reac-- tion can beconductedunder-pressure if so desiredyit is. generally advantageously :carried'oubat atmospheric pressurew Elevated pressures-can-be employedif high reaction temperatures are" desired in connection with =the given solven 111 conducting-the reaction: anatmos'phere s Patented Jan. 1, 1957 can advantageously be employed whereby there will be insuflicient oxygen to substantially oxidize the phenolic hydroxyl radicals so as to avoid any undesirable formation of by-products. Advantageously, a nitrogen atmosphere can be employed. Examples of other inert atmospheres which can be advantageously used include helium, neon, etc. However, no inert atmosphere need necessarily be employed.

Examples of etherification reagents which can be advantageously employed in accordance with the process of this invention include dialkyl sulfates, e. g. diethyl sulfate, dimethyl sulfate, ditertiarybutyl sulfate, etc., alkyl acid sulfates, e. g. propyl acid sulfate, methyl acid sulfate, etc., alkyl chlorides, e. g. isopropyl chloride, methyl chloride, secondary butyl chloride, etc. or alkyl phosphates, e. g. trimethyl phosphate, triethyl phosphate etc. Other compounds which can be advantageously employed in conducting the etherification are readily apparent. An especially advantageous etherification agent is dimethyl sulfate.

In order to produce substantially quantitive yields in accordance with the process described above, the etherification agent is advantageously employed in at least a stoichiometrically equivalent quantity in proportion to the amount of tertiarybutyl hydroquinone employed as a starting material. It has been found that larger proportions (e. g. 1.5 stoichiometrical equivalents) of the etherification agent can also be advantageously employed although there is no purpose to be achieved by using more than about twice the quantity necessary to produce monoetherification. It has been found to be quite advantageous to employ about two thirds more of the etherification agent than is actually required on a stoichiometrical basis.

The reaction is advantageously conducted in the pres ence of a protective material. Most advantageously, the protective material consists of a finely divided or comminuted metal having reducing properties such as zinc or other equivalent metals. In place of zinc other protective materials can be advantageously employed, e. g. Lykopon which consists essentially of sodium hydrosulfite (NazSzOr). Most advantageously zinc dust can be employed. Such a protective material is advantageously employed in minute quantities. When zinc dust is employed, it has been found advantageous to use at least 0.1 percent or up to about 1% or more; generally from about A- to about /2 percent of zinc dust (based on the weight of the mono-tertiarybutyl hydroquinone) can be employed whereby deleterious by-products are substantially completely eliminated. If there is a trace of residual color in the crude reaction product, removal may be made complete by distillation in the presence of about 0.1 percent zinc dust. It is evident that other metallic dusts, other powdered alkali metal hydrosulfites, and other equivalent protective materials can be similarly employed.

The non-aqueous liquid phase of the medium in which the reaction is conducted advantageously contains a solvent selected from the group consisting of aliphatic and aromatic hydrocarbons containing from about 5 to about carbon atoms. Examples of such hydrocarbons include normal pentane, octane, hexane, heptane, benzene, toluene, xylene, mixtures of paraflinic hydrocarbons, straight-run naphthas and various mixtures and solvents of hydrocarbon nature derived from these materials. Other solvents can be similarly employed but those mentioned are generally most advantageously useful. A suflicient quantity of the solvent should be employed to substantially completely dissolve the mixed isomers of tertiarybutyl-4-alkoxyphenol in the reaction product. Generally speaking, about twice the weight of the mono-tertialybutyl hydroquinone of such a solvent can be advantageously employed. Considerable variation in the amount of solvent is obviously permissible.

The amount of water employed in the aqueous liquid phase of the reaction medium is similarly subject to considerable wide variation within reasonable limits. As indicated by the examples set forth below, from 4 to 5 times the weight of the mono-tertiarybutyl hydroquinone of water can be advantageously employed. These examples illustrate amounts of water and solvent which can be used satisfactorily from a practical standpoint. Variations in the amounts of water and solvent, within reasonable limits, do not deleteriously effect the efficacy of the reaction process. An important factor in conducting the process of this invention lies in providing sutficient agitation to effect thorough mixing of whatever amounts of water and solvent are used. This can be accomplished by the stirring, shaking, maintaining reflux conditions, employing other suitable means, etc.

The reaction mixture can be advantageously maintained in an alkaline condition during the course of the reaction by the incorporation of a caustic such as an alkali metal hydroxide, e. g. NaOH, KOH, etc. Advantageously, this alkaline condition is created by introducing a solution of an alkali metal hydroxide in water into the reaction mixture from time to time whereby especially high alkalinity is avoided. Undissolved caustic can also be added. By maintaining the reaction mixture in an alkaline condition, the acid resulting from the etherification reaction is neutralized. The reaction mixture is not allowed to become acidic until after the reaction has been completed.

Advantageously, enough caustic is provided in the reaction mixture so as to neutralize free acid released from the etherification agent. Too much alkalinity tends to increase the formation of the dialkyl ether of tertiarybutyl hydroquinone. Under the conditions of the reaction set forth in the examples given below, it is advantageous to limit the amount of caustic to about a 50% stoichiometrical excess of that needed to neutralize the free acid which might be formed based on the quantity of etherification agent employed, e. g. amounts in excess of 1.92 moles of caustic for each mole of dimethyl sulfate used in the examples below tended to increase the formation of dimethyl ether of mono-tertiarybutyl hydro quinone. As indicated under the reaction conditions set up in the examples, it is preferred to use the amount of caustic given in step-wise addition to the reaction mixture in order to give the most generally advantageous results. Advantageously the caustic added in aqueous solution is purged with nitrogen to remove any oxygen.

The factor of time in regard to the reaction is not critical and can be varied widely depending upon the reaction conditions. The working examples set forth below illustrate useful reaction periods under the reaction periods employed therein.

The reaction product can be separated and purified in various ways other than that illustrated by the examples which set forth an advantageous procedure found to be quite satisfactory in obtaining economical yields.

In conducting the process of this invention, it is advantageous to charge into a reaction vessel mono-tertiarybutyl hydroquinone, the protective agent such as zinc dust, water and a hydrocarbon solvent. The reaction vessel can be advantageously equipped with means for agitation, a reflux condenser, a thermometer and a dropping funnel. It is advantageous to bring the charge in the reaction vessel to a reflux condition providing constant agitation. It is then advantageous to introduce an aqueous solution of a caustic, e. g. sodium hydroxide, into the reaction vessel at such a rate that refluxing is not stopped and the reaction is maintained under alkaline conditions. After the initial introduction of the caustic, the etherification agent can be advantageously introduced over an extended period, e. g., one-half hour (longer or shorter periods can obviously be employed). During the course of the introduction of the etherification agent more caustic can be added, or additional caustic can be introduced after the etherification agent has been added. The reflux conditions are advantageously maintained with continued [agitation for the remainder of the reaction period which is generally of several hours duration. Upon a completion EXAMPLE 1 Materials Monotertiarybutylhydroquinone 830 gms. (0.5 mole). Toluene 250 cc. Dimethyl sulfate 52.5 gms. (0.416 mole). Sodium hydroxide 32.0 gms. (0.8 mole). Water 384 cc. Conc. sulfuric acid 4 cc. Zinc dust 0.5 gm.

Procedure The mono-tertiarybutyl hydroquinone, zinc dust, toluene and 284 cc. of the water were charged to a one liter, 3-necked, round bottom flask and the mixture heated to reflux, with agitation, and refluxed for -15 minutes. Next, a nitrogen purged solution of 21.3 gms. of the sodium hydroxide in 100 cc. of the water was run into the refluxing mixture in 10-15 minutes; then the dimethyl sulfate was added in 30 minutes. One hour after the first of the dimethyl sulfate was added, 10.7 gms. of the sodiurn hydroxide was added to the reaction mixture which was then refluxed 17 hours longer with agitation. The total reaction time was 18 hours and the reaction temperature was 8283.5 C. At the end of the reaction period, the batch was acidified with the sulfuric acid, then the hot toluene layer was separated from the aqueous layer, washed with 100 cc. of hot water, and the solvent removed by distillation at 10 mm. mercury pressure. This dried, crude material was distilled at 10 mm. mercury pressure to give a product which contained 97% mono-tertiarybutyl-4-hydroxy anisole and 3% monotertiarybutyl hydroquinone dimethyl ether. This monotertiarybutyl hydroquinone dimethyl ether was removed from the product as a low-boiler in the distillation.

Of the mono-tertiarybutyl hydroquinone charged as described in Example 1 above, 1.2% remained unreacted, 2.7% was converted to mono-tertiarybutyl hydroquinone dimethyl ether and 93.5% was converted to mono-tertiarybutyl-4-methoxyphenols of the following composition:

Percent 3 tertiarybutyl-4-methoxyphenol 28 2 tertiarybutyl-4-methoxyphenol 72 EXAMPLE 2 Materials Monotertiarybutyl hydroquinone 83.0 gms. (0.5 mole). n-Heptane 250 cc. Dimethyl sulfate 52.5 gms. (0.416 mole). Sodium hydroxide 32.0 gms. (0.8 mole). Water 384 cc. Cone. sulfuric acid 6.8 cc. Zinc dust 0.5 gm.

Procedure This experiment was run exactly like the one given in Example 1 except that n-heptane was used as the solvent, the total reaction time was 14.4 hours and the reaction temperature was 78.5-79 C. The material produced analyzed 92.0% mono-tertiarybutyl-4-methoxyphenol, 6.0% mono-tertiarybutyl hydroquinone dimethyl ether and 2% mono-tertiarybutyl hydroquinone. The conversion of monoetertiarybutyl hydroquinone; for: Example" 2 rani as follows:

87.5 mono-tertiarybutyl-4 rnethoxyphenols 5.3%- mono-tertiarybutyl hydroquinone. dimethyl ether 5.1% unreacted Isomeraratiotofproduct:

28% 3-tertiarybutyl-4-methoxyphenol 72% Z-tertiarybutyl-4-methoxyphenol EXAMPLE 3 Materials Monotertiarybutylhydroquinone 83.0 gms. (0.5 mole). Xylene 250 cc. Dimethyl sulfate 52.5 gms. (0.416 mole). Sodium hydroxide 32.0 gms. (0.8 mole). Water 384 cc. Cone. sulfuric acid 4 cc. Zinc dust 0.5 gm.

Procedure This experiment was run exactly like the one given in Example 1 except that xylene was used as the solvent, the total reaction time was 12.5 hours and the reaction temperature was 90.591.5 C. Also, instead of running under reflux during the reaction period volatile components were removed by slow distillation with replacement of the solvent as distilled. The material produced analyzed mono-tertiarybutyl-4-hydroxy anisole, 4.0% monotertiarybutyl hydroquinone dimethyl ether and 1% monotertiarybutyl hydroquinone. The conversion of monotertiarybutyl hydroquinone for the experiment ran as follows:

89.5% mono-tertiarybutyl-4-hydroxy anisole 3.5% mono-tertiarybutyl hydroquinone dimethyl ether 3.8% unreacted Isomer ratio of product:

28% 3-tertiarybutyl-4-methoxyphenol 72% 2-tertiarybutyl-4-methoxyphonol It is readily apparent that other solvents, other etherification agents and other variations in materials and the various conditions can be employed to obtain results similar to those exemplified by the preceding working examples. Moreover, the process employed can be modified as may be suitable for changes in the various conditions employed. The process can be altered so as to result in the continuous etherification of mono-tertiarybutyl hydroquinone which can be introduced into the reaction zone over an extended period of time along with the introduction of the etherification agent; in such a process a portion of the non-aqueous liquid phase would be removed either continuously or from time to time after the reaction conditions had been maintained for a suitable period of time. In operating according to the continuous process, the conditions described hereinabove would be maintained by suitable addition of water, solvent, etc. as may be required from time to time.

I claim:

1. In a process for oxy-alkylating a nuclearly monoalkylatecl dihydric phenol to form an alkoxy nuclearly monoalkylated monohydric phenol employing a dialkyl sulfate as the oxy-alkylating agent, which process is conducted under reflux conditions and under an inert atmosphere in the absence of an alkylating catalyst, the improvement which consists of oxy-alkylating mono-tertiary butylhydroquinone with a stoichiometric excess of a dialkyl sulfate having from 1 to 4 carbon atoms in each alkyl radical employing a two phase alkaline reaction medium consisting of (1) an aqueous liquid phase maintained in an alkaline condition during the course of the reaction by the introduction of an alkali metal hydroxide and (2) a non-aqueous liquid phase containing a hydrocarbon selected from the group consisting of aliphatic and aromatic hydrocarbons containing from 5 to 10 carbon atoms, whereby there is produced a substantially quantitative yield of a mixture of more than two parts of Z-tertiarybutyl-4-alkoxyphenol together with one part of 3-tertiarybutyl-4-alkoxypheno1.

2. The improvement in a process as defined in claim 1 wherein the oxy-alkylating agent is dimethyl sulfate, the

alkali metal hydroxide is sodium hydroxide and the hydrocarbon is toluene.

References Cited in the file of this patent UNITED STATES PATENTS 

1. IN A PROCESS FOR OXY-ALKYLATING A NUCLEARLY MONOALKYLATED DIHYDRIC PHENOL TO FORM AN ALKOXY NUCLEARLY MONOALKYLATED MONOHYDRIC PHENOL EMPLOYING A DIALKYL SULFATE AS THE OXY-ALKYLATING AGENT, WHICH PROCESS IS CONDUCTED UNDER REFLUX CONDITIONS AND UNDER AN INTER ATMOSPHERE IN THE ABSENCE OF AN ALKYLATING CATALYST, THE IMPROVEMENT WHICH CONSISTS OF OXY-ALKYLATING MONO-TERIARY BUTYLHYDROQUINONE WITH A STOICHIOMETRIC EXCESS OF A DIALKYL SULFATE HAVING FROM 1 TO 4 CARBON STOMS IN EACH ALKYL RADICAL EMPLOYING A TWO PHASE ALKALINE REACTION MEDIUM CONSISTING OF (1) AN AQUEOUS LIQUID PHASES MAINTAINED IN AN ALKALINE CONDITION DURING THE COURSE OF THE REACTION BY THE INTRODUCTION OF AN ALKALI METAL HYDROXIDE AND (2) A NON-AQUEOUS LIQUID PHASES CONTAINING AHYDROCARBON SELECTED FROM THE GROUP CONSISTING OF ALIPHATIC AND AROMATIC HYDROCARBONS CONTAINING FROM 5 TO 10 CARBON ATOMS, WHEREBY THERE IS PRODUCED A SUBSTANTIALLY QUANTITATIVE YIELD OF A MIXTURE OF MORE THAT TWO PARTS OF 2-TERTIARYBUTYL-4-ALKOXYPHENOL TOGETHER WITH ONE PART OF 3-TERTIARYBUTYL-4-ALKOXYPHENOL. 